Genetic Variant NM_001387691.1:c.7C>T (chr7-72925128-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001387691.1(POM121):c.7C>T(p.Pro3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000318 in 1,430,538 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00068 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 8 hom. )

Consequence

POM121
NM_001387691.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.28

Variant links:

Genes affected

POM121 (HGNC:19702): (POM121 transmembrane nucleoporin) This gene encodes a transmembrane protein that localizes to the inner nuclear membrane and forms a core component of the nuclear pore complex, which mediates transport to and from the nucleus. The encoded protein may anchor this complex to the nuclear envelope. There are multiple related genes and pseudogenes for this gene on chromosomes 5, 7, 15, and 22. Alternatively spliced transcript variants encoding different isoforms have been observed. [provided by RefSeq, Jul 2013]

POM121 links:

ENSG00000272843 (HGNC:):

ENSG00000272843 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007335216).

BP6

Variant 7-72925128-C-T is Benign according to our data. Variant chr7-72925128-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657544.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POM121	NM_001387691.1 link	c.7C>T	p.Pro3Ser	missense_variant	Exon 1 of 13	ENST00000434423.5	NP_001374620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
POM121	ENST00000434423.5 link	c.7C>T	p.Pro3Ser	missense_variant	Exon 1 of 13	5	NM_001387691.1	ENSP00000405562.2	Q96HA1-1
POM121	ENST00000395270.5 link	c.-151-1134C>T		intron_variant	Intron 4 of 15	1		ENSP00000378687.1	Q96HA1-3
POM121	ENST00000627934.3 link	c.-151-1134C>T		intron_variant	Intron 3 of 14	5		ENSP00000486504.1	Q96HA1-2
ENSG00000272843	ENST00000608799.1 link	n.-3G>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.000677

AC:

103

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00511

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00287

AC:

AN:

31354

Hom.:

AF XY:

0.00210

AC XY:

AN XY:

18590

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0159

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00151

Gnomad FIN exome

AF:

0.00108

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00108

GnomAD4 exome

AF:

0.000275

AC:

352

AN:

1278302

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

168

AN XY:

627954

show subpopulations

Gnomad4 AFR exome

AF:

0.000241

Gnomad4 AMR exome

AF:

0.0138

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000343

Gnomad4 SAS exome

AF:

0.000895

Gnomad4 FIN exome

AF:

0.000641

Gnomad4 NFE exome

AF:

0.0000241

Gnomad4 OTH exome

AF:

0.000377

GnomAD4 genome

AF:

0.000677

AC:

103

AN:

152236

Hom.:

Cov.:

AF XY:

0.000766

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.00122

ExAC

AF:

0.000598

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

POM121: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0070

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0073

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.3

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.25

MutPred

0.13

Gain of phosphorylation at P3 (P = 0.0063);

MVP

0.13

ClinPred

0.22

GERP RS

3.8

Varity_R

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over